Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Factor VIII (antihemophilic factor) is the protein that is deficient or defective in patients with classical hemophilia and Von Willebrand syndrome. Factor VIII in plasma is thought to be associated in a complex with the highest molecular weight multimers of another glycoprotein, Von Willebrand protein. Highly purified human factor VIII appears to have an Mr of between 200,000 and 300,000 and to consist of several polypeptide chains. The concentration of factor VIII in plasma is around 100-200 ng/ml, equivalent to around 1 nM. The purified proteins retain one or more of the known properties of factor VIII, including the acceleration of factor IXa-mediated activation of factor X, ability to be activated by thrombin and factor Xa, inactivation by activated protein C, and by human antibodies to factor VIII. Among the known clotting factors, factors VIII and V are exceptional in not possessing enzymatic activity. Factors IXa and VIII and X appear to form a functional complex, all of which need to be present and active simultaneously for optimal activation of factor X. The mechanism by which factor VIII promotes activation of factor X by factor IXa is not known, but the major effect is to increase the rate of the reaction. Following treatment of factor VIII with thrombin, a new and smaller polypeptide Mr around 70,000 +/- 5,000 is produced. Factors IXa and Xa also have been reported to activate factor VIII. It is not known whether limited proteolytic cleavage is required absolutely for the expression of factor VIII activity or if it only increases an activity already expressed by the uncleaved protein. Factor VIII is inactivated by thrombin and by activated protein C. Thus, factor VIII can be modulated by at least four of the serine proteases in the clotting system. A major goal for future research is to increase our understanding of the role in blood clotting played by factor VIII, and to apply this information to clinical problems which result from inherited abnormalities of factor VIII.
...
PMID:Factor VIII: structure and function in blood clotting. 642 37

Human factor XII was activated by limited proteolysis with trypsin, and the resulting beta-factor XIIa (Mr = 30,000) was isolated by DEAE-Sephacel column chromatography. The complete amino acid sequence of beta-factor XIIa was then determined on peptides produced by enzymatic digestion with either trypsin, chymotrypsin, or Staphylococcus aureus V8 protease and by chemical cleavage at methionyl and tryptophyl bonds. beta-Factor XIIa is a glycoprotein composed of a heavy chain (243 amino acid residues) and a light chain (9 amino acid residues), and these two chains are held together by a disulfide bond. The carbohydrate is attached to asparagine residue 61 in the heavy chain. The amino acid sequence of the heavy chain shows a high degree of homology to the corresponding regions of other plasma serine proteases, such as plasmin, thrombin, factor IXa and factor Xa, as well as the pancreatic digestive enzymes. These results demonstrate that factor XII is the precursor of a typical serine protease that participates in the coagulation cascade.
...
PMID:Amino acid sequence of human beta-factor XIIa. 660 55

Vipera russellii venom was separated into thirteen fractions by means of DEAE-Sephadex A-50 column chromatography. Fraction III possessed anticoagulant and phospholipase A activities and Fraction XI possessed procoagulant and caseinolytic activities, both were further purified by gel filtration on Sephacryl S-200 column. Purified procoagulant (Component II) was a two-chain protein with molecular weight of 86 000 consisting of A-chain (Mr 66 000) and B-chain (Mr 20 000). It was a glycoprotein containing 7.8% neutral sugar and 715 amino-acid residues. The procoagulant activity was 10-times that of the crude venom. It was an acidic proteinase with isoelectric point of pH 4.2. Upon heat treatment at 60 degrees C, Component II was stable at pH 5.5 and 7.2 for 3 h, but was destroyed completely after 30 min at pH 8.9. It was devoid of esterase or amidase activity. Purified anticoagulant (Component I) was a single peptide chain with molecular weight of 16 000. It was carbohydrate free and contained 136 amino-acid residues. It was a basic protein with an isoelectric point of larger than pH 10. It was a potent phospholipase A with an enzymatic activity of 510 +/- 30 mumol/min per mg using phosphatidylcholine as substrate, and 1 microgram/ml was sufficient to cause 100% hemolysis by the indirect hemolytic method. Upon heat treatment at 90 degrees C, Component I was heat stable at pH 5.5 for more than 3 h, but was destroyed completely after 2 h at pH 7.2 and 8.9. The anticoagulant activity of Component I could be neutralized by platelet factor 3, tissue thromboplastin and cephalin.
...
PMID:Purification and properties of the main coagulant and anticoagulant principles of Vipera russellii snake venom. 672 70

The anticoagulant effect of heparin, as reflected by the slope of the relationship between heparin concentration and the logarithm of the activated partial thromboplastin time (APTT), was determined in citrated plasma of seven women in the third trimester of pregnancy and in 10 nonpregnant women of comparable age. Factors II, V, and VII to XII, albumin, individual globulins, antithrombin III, fibrinogen, alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-2-macroglobulin, prothrombin time, and hematocrit were also determined. Baseline APTT (i.e., APTT without heparin) was 30.2 +/- 3.0 sec (mean +/- SD) in the pregnant women and 29.6 +/- 4.7 sec in the controls (NS). The heparin slope value was 1.68 +/- 0.46 ml/U in the pregnant women and 2.33 +/- 0.49 ml/U in the controls, showing that the anticoagulant effect of heparin is decreased in pregnancy. The prothrombin time was also decreased in pregnancy (19.1 +/- 0.8 vs 23.1 +/- 0.5 sec; P less than 0.01). Pregnancy was associated with a significant increase in the activity of factors VII, VIII, IX, and X and in the concentrations of fibrinogen, alpha-1-globulin, and alpha-1-antitrypsin. The plasma albumin concentration was decreased in the pregnant group. In both the pregnant and nonpregnant women (considered separately), the heparin slope value correlated negatively with factor XI activity (r = -0.85 and -0.71; P less than 0.05). Baseline APTT, which was consistently found to correlate with heparin slope value in previous reports on men and nonpregnant women, also showed such correlation in the nonpregnant group of the present study (r = 0.85; P less than 0.05) but not in the group of pregnant women (r = -0.54; NS). The relative heparin resistance in pregnancy in this investigation is consistent with clinical reports of increased heparin requirements during pregnancy.
...
PMID:Effect of pregnancy on the relationship between concentration and anticoagulant action of heparin. 686 35

alpha 1-Acid glycoprotein (AAG) obtained from ascites and/or pleural fluids exhibited anti-heparin effects in platelet-poor plasma when evaluated by activated partial thromboplastin (Activated Thrombofax Reagent) and heparin-thrombin clotting time assays. An anti-heparin effect for AAG was also demonstrable in platelet-rich plasma (PRP) challenged with thrombin, but only over a limited range of heparin concentrations; at elevated heparin concentrations, and only in the presence of AAG, both platelet aggregation and clot formation were substantially inhibited. However, no detectable anti-heparin effect was observed following challenge of PRP with Activated Thrombofax Reagent; indeed, the anti-coagulant effect of heparin appeared synergistically amplified in these systems containing AAG, and AAG exhibited platelet pro-aggregate and pro-coagulant properties in the absence of heparin. The platelet pro-aggregating activity of AAG, though independent of heparin, appeared to require the onset of the coagulation cascade prior to the generation of thrombin; in the absence of such initiation, AAG remained a potent inhibitor of platelet activation.
...
PMID:Effects of heparin and alpha 1-acid glycoprotein on thrombin or Activated Thrombofax Reagent-induced platelet aggregation and clot formation. 687 53

We have isolated a previously unrecognized heparin-dependent inhibitor of thrombin from human plasma. The inhibitor, designated heparin cofactor II (HCII), was purified to homogeneity with sulfated-dextran, DEAE-Sepharose, heparin-Sepharose and Sephadex G-150. HCII is a glycoprotein consisting of a single polypeptide chain with a Mr = 65,600 as determined by sedimentation equilibrium analysis. Other physical properties include s20,w = 4.31 S; Stokes radius = 34 A; E280 1% = 11.7; and pI = 4.95 to 5.15. The purified inhibitor is not precipitated by antibodies directed against seven other plasma protease inhibitors, including antithrombin III (ATIII). HCII blocks the proteolytic and amidolytic activities of thrombin by forming a covalent, 1:1 molar complex with the protease. The second-order rate constant for inhibition of thrombin by purified HCII increases from 5.0 X 10(5) M-1 min-1 in the absence of heparin to 4.5 x 10(8) M-1 min-1 at optimal heparin concentrations of 0.8 to 1.0 unit/ml. In comparison with ATIII, HCII is a relatively ineffective inhibitor of coagulation factor Xa.
...
PMID:Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma. 689 93

Wheat germ agglutinin (WGA) and concanavalin A (Con-A) (also red kidney bean agglutinin, PHA) have been found to be inhibitors of plasma clotting in vitro. At 40 micrograms/ml and 250 micrograms/ml (4.4 MicroM and 10 microM in carbohydrate binding sites, final concentrations) respectively, WGA and Con-A are able to double the activated partial thromboplastin time of normal human control plasma. Their inhibitory effect is due to their capacity to interact with the carbohydrate portion of blood clotting factors. It is totally abolished in the presence of specific saccharides for WGA or Con-A and is attenuated in the presence of 4% (v/v, final concentration) of human erythrocytes. The action of WGA is mediated by its ability to interact with N-acetylneuraminic acid. When purified phospholipid vesicles plus kaolin are used as an activator instead of cephalidin, this effect persists to the same extent. These two lectins also prolong the plasma clotting time using Russell's viper venom plus purified phospholipid vesicles as an activator. Quick's time was also prolonged by WGA and Con-A but to a lesser extent in this case. WGA can interact directly with some purified blood clotting factors (IX, X and II) in a classical lectin-glycoprotein precipitin reaction. When assessed at individual factors level in whole plasma using clogging assays, direct inhibitions by WGA are only apparent.
...
PMID:Reversible inhibition of the in vitro coagulation of human plasma by lectins. 689 62

The anticoagulant effect of heparin as reflected by the slope (S) of the relationship between heparin concentration and natural log of activated partial thromboplastin time (APTT) was determined in citrated plasma of 31 hospitalized, 21- to 80-yr-old patients (including many typical candidates for heparin therapy). Also determined were level of factors II, V, VII to XII, albumin, individual globulins, calcium, antithrombin III, fibrinogen, alpha-1-acid glycoprotein, alpha-1-antitrypsin, and alpha-2-macroglobulin and prothrombin time and hematocrit. Baseline APTT was 24.1 to 60.3 sec and S was 1.80 to 4.27 ml/u. S correlated with baseline APTT, hematocrit, total protein, functional antithrombin III, prothrombin time, beta-globulin, and factors II, VII, X, XI, and XII. A multiple linear regression equation with baseline APTT, total protein concentration, and factor XI as independent variables was "best" for predicting the S of these patients (r = 0.807, P less than 0.0001). A multiple linear regression equation with baseline APTT and hematocrit as independent variables, obtained in a previous study on healthy subjects, overpredicted the patients' S values. An equation with baseline APTT and gamma-globulins as independent variables yielded the best correlation predicted and actual S values for the combined group of patients and normal subjects (r = 0.715, P less than 0.0001). Our observations indicate that it may be possible to predict the heparin concentration-anticoagulant effect (APTT) relationship for individual patients before institution of heparin therapy.
...
PMID:Relationship between concentration and anticoagulant effect of heparin in plasma of hospitalized patients: magnitude and predictability of interindividual differences. 711 66

The purpose of this study was to investigate the effect on coagulation of alpha-acid-glycoprotein, one of the acute-phase reactants, the blood level of which is elevated in malignant disease and various acute conditions. Alpha-acid-glycoprotein was obtained from serum and plasma of normal volunteers. The amount obtainable from serum was greater than that obtained from plasma (43 mg/dl v. 22 mg/dl), and differences were noted in the molecular weight of the two preparations; alpha-acid-glycoprotein from serum had a molecular weight of 55 000, while that from plasma appeared to have a molecular weight of 81 000. The two preparations were identical in their reactivity towards anti-alpha-acid-glycoprotein. Alpha-acid-glycoprotein markedly shortened the partial thromboplastin time (PTT), but no effect on prothrombin index was noted. At those concentration which shortened the PTT, the preparation was able partially to reverse the anticoagulant activity of heparin. The possibility that this protein plays a role in the aetiology of coagulation disorders in cancer is discussed.
...
PMID:The effect of seromucoid on coagulation. 728 Aug 87

The heparin-antagonizing effect of human alpha 1-acid glycoprotein (alpha 1-acid GP) was studied by activated partial thromboplastin time (APTT) and by a factor Xa assay for heparin using a chromogenic substrate for factor Xa. The antiheparin effect of alpha 1-acid GP in the APTT system was similar to the effect on heparin thrombin clotting time (HTCT), and the effect in the factor Xa assay system corresponded well with the effect in a heparin cofactor assay system using chromogenic substrate for thrombin instead of factor Xa. It is concluded that alpha 1-acid GP contributes to the reduced anticoagulant effect of heparin observed in various acute stages of disease, when assayed not only by HTCT but also by so-called 'global' coagulation tests, such as the activated partial thromboplastin time.
...
PMID:The antiheparin effect of alpha 1-acid glycoprotein, evaluated by the activated partial thromboplastin time and by a factor Xa assay for heparin. 740 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---